Am J Clin Exp Immunol 2012;1(1):12-19.
Pregnancy amelioration of arthritis in SKG mice corresponds with
alterations in serum amyloid A3 levels
Laura A Shaw, Adrianne L Stefanski, Lisa K Peterson, Kristen K Rumer, Andrea Vondracek, Tzu L Phang, Shimon
Sakaguchi, Virginia D Winn, Leonard L Dragone
Department of Pediatrics, National Jewish Health, Denver, Colorado 80206; Department of Obstetrics and Gynecology,
University of Colorado, Aurora, Colorado 80045; Graduate Program in Reproductive Sciences, University of Colorado,
Aurora, CO 80045; Department of Medicine, University of Colorado, Aurora, CO 80045; Computational Bioscience
Program, University of Colorado, Aurora, CO 80045; Institute for Frontier Medical Sciences, Kyoto University, Kyoto,
Japan; WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Department of Pediatrics, University
of Colorado, Aurora, Colorado, 80045; Division of Rheumatology, The Children’s Hospital, Aurora, Colorado 80045;
Integrated Department of Immunology, National Jewish Health, Denver, Colorado 80206; * co-first authors, # co-last
Received February 20, 2012; accepted March 29, 2012; Epub April 20, 2012; Published June 30, 2012
Abstract: Objectives: Pregnancy leads to rheumatoid arthritis remission in humans. The objective of this study was to
determine if the SKG mouse could serve as a model for pregnancy-associated inflammatory arthritis amelioration. In
addition, the maternal peripheral blood mononuclear cell (PBMC) transcriptome was assessed to define a biomarker
associated with remission. Methods: Cohorts of zymosan-treated pregnant SKG mice and controls were monitored for
arthritis progression. Microarray analysis evaluated alterations in gene expression in maternal PBMCs at embryonic day
14.5 (E14.5) between arthritic and pregnancy-remitted mice. A selected target, serum amyloid A3 (SAA3), was further
investigated using quantitative reverse transcriptase PCR (qRT-PCR) and an enzyme-linked immunosorbent assay
(ELISA). Results: Pregnancy resulted in complete or partial remission in the majority of the zymosan-treated SKG mice.
Twenty-seven transcripts were differentially expressed in the PBMCs between arthritic and pregnancy-remitted mice.
Expression and plasma SAA3 levels decreased with pregnancy-induced arthritis amelioration and plasma SAA3 levels
correlated with arthritis severity. Conclusions: These results establish the SKG mouse as a model system to study
pregnancy-induced amelioration of arthritis. These studies also establish SAA3 as a biomarker of arthritis amelioration
in SKG mice. This model can be used to elucidate the molecular and cellular mechanisms underlying the impact of
pregnancy on the maternal immune system that results in arthritis amelioration. (AJCEI1202001).
Keywords: SAA3, rheumatoid arthritis, microarray, pregnancy, SKG mouse
Address all correspondence to:
Leonard L. Dragone, MD, PhD
Department of Pediatrics, National Jewish Health
1400 Jackson Street, Room K1026, Denver, CO 80206
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